Apparatus for characterizing a vessel wall

ABSTRACT

The invention presents an apparatus (6) for characterization of a condition of a vessel (12) wall of a living being (2). The relationship between temporal blood pressure (621) and blood flow (622) measurements of pulsatile blood motion within the vessel (12) is an indication of the health of the vessel (12) wall. Furthermore, the invention discloses a system (1) comprising the apparatus (6), and a method (100) of characterizing the condition of vessel (12) walls.

FIELD OF THE INVENTION

The invention relates to an apparatus, a system and a method formeasuring physical properties inside a body lumen.

BACKGROUND OF THE INVENTION

Weakening of an arterial wall may lead to formation of a bulge on thevessel wall. A large fraction of the population has asymptomaticaneurysms with no further growth of the bulge, presenting low risk fortheir condition. However, when the aneurysm evolves in size, thearterial wall weakens beyond a critical threshold due to the pressureexerted by the increasing volume of blood, resulting in rupture of thearterial wall and subsequent internal hemorrhage. After formation of ananeurysm, assessment of several physical properties as predictors of theaneurysm growth as well as the dynamic assessment of the physicalproperties inside the aneurysm pouch are crucial in understanding andpredicting progression of the aneurysm and the associated risk ofarterial wall rupture. Blood flow pattern assessment and local bloodpressure measurements are supporting the physicians in taking a decisionwhether an aneurysm requires treatment. Typical treatments compriseplacing coils into the aneurysm for breaking the flow pattern that isstretching the arterial wall, placement of blood flow diverters in thelumen of the arterial wall for impeding blood flow into the aneurysm, ora combination of the two in various phases of the treatment process.

Computational Fluid Dynamics (CFD) modeling by integratingpatient-specific intravascular blood flow velocity and pressuremeasurements into computational models of aneurysms before and aftertreatment with flow-diverting stents is presented in “Cerebral AneurysmsTreated with Flow-Diverting Stents: Computational Models withIntravascular Blood Flow Measurements” by M. Levitt et al., AmericanJournal of Neuroradiology, Vol. 35, issue 1, pages 143-148. The premiseof aneurysmal flow diversion is the reduction of blood flow into theaneurysm dome, promoting intra-aneurysmal thrombosis and promotingendothelialization of the stent wall, which reconstructs the parentvessel, excluding the aneurysm. Reduction of hemodynamic stress isbelieved to be crucial in achieving this goal, and the determination ofsuch stress is an important application of CFD analysis. In the methodof hemodynamic stress computation three-dimensional rotationalangiography is used, obtained before aneurysm treatment of patients.Contrast-enhanced flat panel Computer Tomography (CT) was obtained forstent visualization after treatment by endovascular flow-diverting stentplacement. Blood flow velocity and blood pressure were measured beforeand after placement of flow-diverting stents by use of a dual-sensorpressure and Doppler velocity guidewire at essentially the samelocations. The measurements were exported to a workstation for CFDanalysis where the three-dimensional reconstructions of the vessels werecreated from the rotational angiographic images. A “virtual stent” wasplaced into each reconstruction for posttreatment simulations byinserting a saddle-shaped surface to the location of the stent boundaryon the basis of its location in the posttreatment CT. In accordance withthe therapeutic intent of flow-diverting stents, the results of the CFDmodel showed reduction of flow rate, vessel wall shear stress and shearstress gradient in the aneurysmal domes after treatment.

US 2005/0197571 A1 discloses an apparatus and method for the measurementof vascular impedance of the ocular circulation in vivo are provided. Apressure pulse waveform is recorded from measurement of the intraocularpressure, and the velocity profile of blood flow in the retrobulbarcirculation is recorded. These two readings are used to calculate thevascular impedance modulus.

SUMMARY OF THE INVENTION

It is an object of the invention to provide an apparatus for improvedcharacterization of a condition of a vessel wall of a living being.

According to a first aspect of the invention, this object is realized byan apparatus for characterizing a condition of a vessel wall of a livingbeing, the apparatus comprising:

a processor for processing measurement signals, wherein the apparatus isconfigured to receive a temporal pressure measurement signal and atemporal flow measurement signal of a pulsatile blood motion within avessel from at least an instrument trackable by an imaging unit withrespect to a morphology of the vessel, and wherein the processor isconfigured to

ascertain a phase difference between the temporal pressure measurementsignal and the temporal flow measurement signal, indicative of thecondition of the vessel wall.

A phase difference between a pulsatile blood pressure measurement signaland a pulsatile blood flow measurement signal within the vessel appearsto be sufficient for a discrimination of a healthy vessel wall from aweakened one. This provides simplicity and an improved indication ofvessel wall condition over flow pattern analysis based on CFD usingangiographic information.

In a second aspect of the invention, a system for characterizing acondition of a vessel wall of a living being is presented, the systemcomprising:

the apparatus according to the invention,

the at least an instrument configured for providing the temporalpressure measurement signal of the pulsatile blood motion within thevessel, and

the imaging unit configured for providing morphological information ofthe vessel,

wherein the imaging unit or the at least an instrument is configured forproviding the temporal flow measurement signal of the pulsatile bloodmotion within the vessel.

The pulsatile blood pressure measurement signal may be provided by apressure sensor integrated into an interventional instrument, whereasthe pulsatile blood flow measurement signal may either be a volumetricflow measurement with a suitable imaging unit or a blood flow velocitymeasurement provided by a suitable sensor integrated into theinterventional instrument. The imaging unit may provide radiographicprojections, computed tomography, ultrasound or magnetic resonance basedmorphological information. A weakened wall segment of the vessel can beidentified and tagged on the display by tracking the position of theinstrument with respect to the morphology of the vessel, and by knowingthe phase difference between the pulsatile blood pressure and thepulsatile blood flow.

In an embodiment, the system further comprises a display, and theprocessor is configured for rendering a representation of the phasedifference between the temporal pressure measurement signal and thetemporal flow measurement signal on the display, indicative of thecondition of the vessel wall. The visual representation of the phasedifference may be a graphical representation of a superposition of thetemporal pressure and flow measurement signals, a value indicating thephase difference in radians or a percentage of the phase differencerelative to the period of the pulsatile blood motion.

In a further embodiment of the system, the processor is configured forrendering a morphological representation of the vessel on the displayfrom the morphological information provided by the imaging unit. Thestructure of the vessel provides essential information for the physicianduring navigation of interventional instruments through vessels, inorder to reach target sites in remote vasculature, for instance when thesites are located in peripheral and cerebral vasculature.

In a third aspect of the invention, an instrument for providing temporalpressure and flow measurement signals of a pulsatile blood motion withina vessel is presented, the instrument connectable to the apparatusaccording to the invention, the instrument comprising a pressure sensorand a flow sensor, wherein the pressure sensor and the flow sensor arelocated such as to provide temporal pressure and flow measurements in asame transversal plane of the instrument, wherein a position of theinstrument is trackable by an imaging unit with respect to a morphologyof the vessel. The benefit of using one and the same instrument forblood pressure and blood flow measurement, with sensors located in thesame transversal plane of the instrument, is that in the process ofascertaining the phase difference between pulsatile pressure and flow,one can neglect the phase difference offset that would originate fromthe distance between the two measurement points along the blood vessel.

In a fourth aspect of the invention, a method of characterizing acondition of the vessel wall of the living being is presented, themethod comprising:

receiving temporal pressure and flow measurement signals of a pulsatileblood motion within a vessel from at least an instrument trackable by animaging unit with respect to a morphology of the vessel, and

ascertaining a phase difference between the temporal pressuremeasurement signal and the temporal flow measurement signal, indicativeof a condition of the vessel wall.

In an embodiment, the method further comprises the step of rendering arepresentation of the phase difference between the temporal pressuremeasurement signal and the temporal flow measurement signal on adisplay, indicative of the condition of the vessel wall. Graphical ornumerical visualization of the phase difference boosts visualinterpretation of the results and improves assessment of the conditionof the vessel wall segments.

In a further embodiment, the method comprises the steps of tracking aposition of the at least an instrument with respect to the morphology ofthe vessel, and displaying the position of the at least an instrument onthe morphological representation of the vessel. Position tracking of themeasurement instrument with respect to the morphology improves thelocalization of the segments with weakened vessel wall, and providessupporting information for treatment decisions of those segments.

In yet a further embodiment, the method comprises positioning of the atleast an instrument distal to an aneurysm with respect to a direction ofthe blood motion within the vessel based on tracking the position of theat least an instruments with respect to the morphology of the vessel.The method allows detection of an aneurysm in a vessel and evaluation ofpotential risks associated to vessel wall weakness.

In an embodiment, the method further comprises positioning of the atleast an instrument distal to a flow diverting stent that is impeding atleast partially blood flowing into the aneurysm based on tracking theposition of the at least an instruments with respect to the morphologyof the vessel. Flow diverting stents reduce hemodynamic stress of thealready weak vessel wall of the aneurysm. The partial or completeocclusion of the aneurysm promotes intra-aneurysmal thrombosis andendothelialization of the stent wall. The outcome of flow divertingstent apposition can be efficiently evaluated from the phase differencebetween the pulsatile blood pressure and pulsatile blood flowmeasurement signals.

In a further embodiment, the method is used for vessel comprising coilsinside the aneurysm. The long-term clinical outcome assessment of such atreatment and the risk evaluation for growth of the aneurysm based onCFD flow simulations relying on angiography are seriously hindered bythe presence of coils in the aneurysm. Therefore, the method offersimproved characterization of the condition of the vessel wall after coilplacement into the aneurysm.

In an embodiment of the method, the temporal pressure and flowmeasurement signals are originating at the same distance from a neck ofthe aneurysm based on tracking the position of the at least aninstruments with respect to the morphology of the vessel. The advantageis that there is no need for compensation for the temporal offset in thephase difference between pressure and flow measurement signals caused bythe dissimilar distances between the locations of the pressure and flowmeasurements with respect to the weakened vessel wall.

Additional aspects and advantages of the invention will become moreapparent from the following detailed description, which may be bestunderstood with reference to and in conjunction with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings:

FIG. 1 shows schematically and exemplarily an embodiment of a systemaccording to the invention.

FIG. 2 shows schematically and exemplarily an embodiment of aninstrument used for characterization of a vessel wall.

FIG. 3 shows an exemplary embodiment of the distal tip of theinstrument.

FIG. 4 shows an alternative embodiment of the distal tip.

FIG. 5 shows an exemplary angiographic projection of a vasculature.

FIG. 6 shows an exemplary three-dimensional vessel morphologyrepresentation of a region from the angiographic projection.

FIG. 7 shows schematically and exemplarily an embodiment of anequivalent electrical circuit of a vasculature network.

FIG. 8a shows an exemplary vessel morphology representation of a vesselwith healthy vessel walls.

FIG. 8b shows an exemplary representation of a pulsatile blood pressureand a pulsatile blood flow measurement for a vessel with healthy vesselwalls.

FIG. 9a shows an exemplary vessel morphology representation of a vesselcomprising an aneurysm.

FIG. 9b shows an exemplary representation of the pulsatile bloodpressure and pulsatile blood flow measurements for a vessel comprisingan aneurysm.

FIG. 10a shows an exemplary vessel morphology representation of a vesseltreated by flow diverting stent apposition.

FIG. 10b shows an exemplary representation of the pulsatile bloodpressure and pulsatile blood flow measurements for a vessel treated byflow diverting stent apposition.

FIG. 11 shows an exemplary vessel morphology representation of a vesseltreated by placement of coils into the aneurysm prior to apposition of aflow diverting stent.

FIG. 12 shows schematically a method for characterizing the condition ofthe vessel wall of a patient.

DETAILED DESCRIPTION OF EMBODIMENTS

FIG. 1 shows schematically and exemplarily an embodiment of a system 1according to the invention, used for characterization of a condition ofa vessel wall of a living being 2. In this embodiment, the systemcomprises a radiological imaging unit 3 for acquiring radiologicalangiographic (RA) projection of the vessel structure of interest uponinjection of a contrast agent bolus in the targeted vasculature. Theradiological imaging unit 3 comprises an x-ray source 31 for emittingx-rays 32 traversing the person 2 lying on the support means 4. Theradiological imaging unit 3 further comprises an x-ray detector 33 fordetecting the x-rays 32 after having traversed the person 2. The x-raydetector 33 is adapted to generate detection signals being indicative ofthe detected x-rays 32. The detection signals are transmitted to afluoroscopy control unit 34, which is adapted to control the x-raysource 31, the x-ray detector 32 and to generate two-dimensionalmorphological projection information depending on the received detectionsignals. The injection of the radiological contrast agent bolus in thetargeted vasculature is performed trough a lumen of the instrument 5,the lumen extending from the handgrip 51 to the distal tip 52 positionedat the target site in the vasculature. Alternatively, the instrument 5may be introduced into the vasculature through the lumen of a tubularsheath, and the tubular sheath may be used for injection of theradiological contrast agent. Two-dimensional or three-dimensionalmorphology of the vasculature can be obtained with various techniquessuch as: magnetic resonance angiography (MRA) in which the imaging unit3 is a magnetic resonance imaging system and the contrast agent is agadolinium-based substance; ultrasound imaging (UI) in which thevasculature is imaged by using an extracorporal or intracorporalultrasound imaging unit 3 while an echogenic contrast agent comprisingmicrobubbles enhances the visibility of the vessels carrying blood; andcomputed tomography angiography (CTA) which is similar to RA. Theinstrument 5, which may be an interventional catheter, further comprisestwo sensors on its distal portion for providing measurement signals ofphysical properties of the blood within the vessel. An apparatus 6receives the measurement signals and is adapted to renderrepresentations of the measurement signals or derived quantities on adisplay 61. The apparatus 6 may further be configured to render arepresentation of the morphology of the vessel on the display 61.

FIG. 2 shows an exemplarily embodiment of an instrument 5 used forassessment of the condition of the vessel wall. The instrument comprisesa handgrip 51, a tubular elongated shaft 54, an extensible and moreflexible shaft 53 reaching distal to the tubular elongated shaft 54, aconnection cable 56 and a connector 55 for connecting the instrument tothe apparatus 6. Alternatively, the instrument 5 may be only a guidewirecomprising the flexible shaft 53, and the cable 56 may be a continuationof the guidewire, terminating at the proximal end with a connector 55that is connectable to a patient interface module. In the guidewireconfiguration the instrument 5 is inserted into the vasculature of thepatient through the lumen of an introducer sheath comprising the tubularhandgrip 51 and the tubular elongated body 54. In the distal end 52 ofthe instrument 5 two sensors are integrated, a pressure sensor 521 and aflow sensor 522, similar to the configuration of the ComboWire® XTguidewire manufactured by Volcano Corporation. Typical pressure sensorsuse change of piezoresitive property upon pressure, fluidic transductionof a deflection of a diaphragm to a mechanical or an electrical signal,and capacitive readout of a suspended membrane over a substrate. Flowsensors integrated in interventional medical instruments typically useDoppler effect of ultrasound or laser radiation to measure blood flowvelocity in vessels. The ultrasound waves for blood flow velocitymeasurement may be generated by piezoelectric ceramic (PZT) or plastic(PVDF) materials, as well as by capacitive or piezoelectricmicromachined ultrasound transducers (cMUT or pMUT).

In FIG. 3 an alternative embodiment of the distal tip 52 isschematically illustrated in a partial cross section of the instrument.A cMUT pressure sensor 521 comprising a membrane facing sideward isintegrated into the distal tip 52, for allowing blood exerting pressureon the membrane. A piezoelectric ultrasound transducer 522 facing distalto the instrument is integrated for flow velocity measurement in theaxial direction. A transversal plane 526 is defined by the longitudinalaxis 525 of the cMUT pressure sensor. The sensors measure blood flowvelocity and blood pressure in the same transversal plane 526 of theinstrument 5, hence by placing the instrument into a vessel lumen thenalso in a single transversal plane of the vessel.

An alternative embodiment of the distal tip 52 is schematicallypresented in FIG. 4. The piezoresistive pressure sensor 521 isintegrated such that it measures blood pressure in a transversal plane526 comprising the distal end 527 of the instrument 5. The pulsatileblood flow velocity is measured with an optical sensor comprising anoptical fiber 523 integrated into the instrument. In this embodiment,the apparatus comprises a source for generating laser radiation that istransmitted through the optical fiber 523 to the distal portion 52 ofthe instrument. An optically transparent cavity 528 may separate thedistal end of the optical fiber from the distal end 527 of theinstrument. The cavity 528 may be of glass, transparent plastic or acompartment filled with optically transparent fluid. The apparatus 6shown in FIG. 1 comprises a detector which detects the optical signalsreflected back from the moving blood, and the processor derives theblood flow velocity from the frequency shift of the received laserradiation with respect to the transmitted one. Alternatively, theoptical fiber 523 can be used for pressure measurement when theoptically transparent cavity comprises a flexible membrane at the distalend 527 of the instrument. The pressure exerted on the distal end of theinstrument causes a deflection of the membrane, and the optical pathchange of the laser reflection from the membrane is a measure of theexerted pressure for a known bending stiffness of the membrane. Theoptical path change may be measured by interferometry, wherein thereference optical path is defined by the reflection from the distal endof the optical fiber 823, and the changing optical path is defined bythe reflection from one of the surfaces (internal or external) of themembrane closing the cavity at the distal end 527 of the instrument. Asa further alternative, the single optical fiber 523 and the cavity 528sealed by the membrane at the distal end 527 of the instrument 5 may beused simultaneously for blood pressure and blood flow velocitymeasurements, the deflection of the semitransparent membrane is themeasure of the blood pressure exerted on the membrane, and the frequencyshift of the laser radiation resulting from the motion of the blooddistal to the instrument 5 is the measure of the blood flow velocity.

Although the pulsatile blood pressure has to be measured locally in thelumen of the vessel, the pulsatile blood flow can be derived from RA,CTA, MRA and UI. As an example, the pulsatile blood flow derived from RAis disclosed in Bonnefous et al, “Quantification of arterial flow usingdigital subtraction angiography”, Medical Physics, Vol. 39, No. 10, p.6264-75, 2012. The technique involves injection of iodine contrastmedium at a very modest rate (e.g. 1.5 ml/s) into the vessel. As aconsequence, the contrast agent is modulated by the flow pulsatility atthe injection point driven by the cardiac cycle. The contrast is denserduring the diastole phase and less dense during the systole phase. Themodulated contrast agent pattern travels through the vessels. In thex-ray image, the contrast agent patterns can be followed along thevessel trajectory using an optical flow algorithm. By matching a 3Dreconstruction of the vessel tree (e.g., obtained by 3D-RA) with thex-ray images, foreshortening can be taken into account, and the vesseldiameters can be calculated.

To determine the flow, the low frequent in- and out-flow of contrastmedium is separated from the high frequent pulsatile components. Theflow measurements need to be temporally synchronized to the pressuremeasurements from the instrument 5, which can be realized bysynchronizing the injection of the contrast agent into the vessel withthe pressure measurement. Optionally, it is possible to inject thecontrast agent with the same system that measures the blood pressure(e.g. one unified guiding catheter/pressure guidewire assembly).

FIG. 5 shows an angiographic projection 10 of a branching vessel, with aleft branch 11 and a right branch 12. The right branch 12 comprises aloop and a bulge in the region 13 marked with a circle, for theexemplary description of the invention. A magnified three-dimensionalvessel morphology representation 20 of the region 13 is reconstructedbased on angiographic projections, which shows in FIG. 6 that the rightvessel branch 12 comprises a region with weakened vessel wall that ledto formation of an aneurysm 14. Typically, the aneurysm presents acircumferential neck 15, which represents the segment of weakened vesselwall. The three-dimensional model may further allow the possibility tocustomize a flow diverting stent 16 for treatment planning

The vascular system can be represented in a simplified form as anequivalent electrical circuit of resistors and capacitors, whereby thevessels are represented by resistors and the aneurysms are representedby capacitors. The resistance of a single vessel is determined by itsradius and its length. A vessel network can be collapsed into a singleresistor. The capacity of the aneurysm is determined by its volume, itsneck 15 area and its position. A vascular network with an aneurysm canbe modelled as illustrated in FIG. 7. The oscillating source Srepresents the heart, which is the source of the periodic blood pressurewith electrical equivalence of a potential, and the periodic blood flowwith electrical equivalence of a current. Resistors R₁, R₂ and R₃represent the resistance of the entire vascular network proximal to theaneurysm, the resistance of the vessel segment that holds the aneurysm14, and the resistance of the entire vascular network distal to theaneurysm, respectively. Capacitor C models the influence of the aneurysm14 on the blood flow. The complexity of the network may further beincreased by addition of elements to the equivalent electrical circuit.

For a healthy vessel wall, schematically illustrated in FIG. 8a , thecapacitor C is missing from the electrical network, due to the absenceof an aneurysm. The blood pressure and blood flow are measured at theposition of the sensors 521 and 522 in the vessel 12 with the instrument5. Alternatively, the blood flow can be derived for the position of theblood pressure sensor from RA, CTA, MRA or UI, in which case theinstrument 5 comprises only the pressure sensor 521, and the blood flowmeasurements are temporally synchronized to the pressure measurements.For a healthy vessel segment the current and the potential representingthe blood flow and the blood pressure respectively, are in phase acrossthe resistor R₂, as exemplarily illustrated in FIG. 8b . The pulsatilemotion with a period T 620 is generated by cyclical heartbeat. Thecontinuous line 621 represents the temporal blood pressure measurementsignal and the dotted line 622 represents the temporal blood flowmeasurement signal.

FIG. 9a shows an example of an aneurysm 14 formed due to a weakenedsegment of the vessel wall. The position of the distal tip 52 comprisingthe sensors 521,522 is distal to the aneurysm with respect to thedirection of blood flow. Preferably, the measurement signals originateat the same distance from the neck 15 of the aneurysm 14, which can beprovided with one of the embodiments of the instrument 5 shown in FIGS.3, 4 or by a typical pressurewire (e.g. Verrata® Pressure Guide fromVolcano Corporation) and one of the modalities from RA, CTA, MRA and UIused for deriving pulsatile blood flow.

The presence of the aneurysm causes a phase difference At 630 betweenthe measured blood pressure 621 and measured blood flow 622, asillustrated in FIG. 9b , similar to the phase difference between thepotential and current measured between the resistors R₂ and R₃ in theequivalent electrical circuit. The measure of the phase difference isindicative of the condition of the vessel wall, hence the size of theaneurysm. For detection of the phase difference 630 it is not essentialto accurately measure the absolute values of pulsatile blood pressureand pulsatile blood flow, since the pulsatility is easily derivable fromrelative blood pressure and blood flow measurement signals. Therefore,calibration of the measurements is not necessary, which is a majoradvantage of the technique.

Typical treatment of an aneurysm is flow diverting stent apposition intothe vessel, such that the weakened vessel segment and adjacent portionsproximal and distal to the weakened segment are covered and protectedfrom further weakening. FIG. 10a shows an example of a stent 16 limitingblood flowing into the aneurysm 14. The stent prevents in the firstinstance the evolution of the aneurysm to a larger size, leading toincreased risk of aneurysm rupture, and secondly, it permits the bloodalready present within the aneurysm to clot and form further protectionof the already weak vessel wall. Placing a flow diverting stent 16reduces the capacitance C of the aneurysm in the equivalent electricalcircuit, with the consequence that the phase difference between thepotential and the current reduces. FIG. 10b shows the effect of a flowdiverting stent apposition on the measured blood pressure 621 and bloodflow 622. The change of the phase difference prior and post flowdiverting stent apposition (630 compared to 631) is a measure of stentplacement efficacy, as an incorrectly placed stent has less impact onthe capacitance C of the aneurysm 14. The expected outcome of thetreatment is that the aneurysm stops evolving, and the clotted bloodcompletely blocks and protects the wall of the aneurysm. Therefore, in afollow-up examination of the patient, the phase difference 631 isexpected to further decrease, potentially showing no phase differenceafter a longer duration.

An alternative, but less efficient treatment of the aneurysm isplacement of multiple coils within the aneurysm, with the intent tolimit blood flowing into the aneurysm by decreasing the available volumeof the aneurysm pocket. In case that the treatment is not successful andthe aneurysm keeps evolving in size, flow diverting stent apposition isnecessary. The coil placement is just very locally addressing theproblem, whereas the flow diverting stent protects vessel wall segmentsproximal and distal to the aneurysm, which might also exhibit poorcondition. An example of an aneurysm 14 treated by placement of coils 17prior to flow diverting stent 16 apposition is shown in FIG. 11, whereinthe aneurysm in the vessel model has been partially sectioned for makingcoils 17 visible in the illustration.

Once the processor ascertains the phase difference 630, 631 between themeasured pulsatile blood pressure 621 and pulsatile blood flow 622signals, the processor may render a graphical representation aspresented in FIGS. 8b, 9b, 10b on the display 61 integrated into theapparatus 6, or on a separate screen available for the physician.Alternatively or additionally, the display may present valuescorresponding to the phase difference At, or a percentage of the phasedifference with respect to the period T between consecutive heartbeats.The processor may render on the display 61 a morphologicalrepresentation 20 of the vessel structure from information received fromthe imaging unit 3. The imaging unit 3 may further provide informationon the position of the instrument 5 with respect to the morphology ofthe vasculature. Tracking of the distal tip 52 of the instrument 5 in RAor in CTA can be achieved by using radiological marker integrated intothe distal tip. Alternatively, in UI the tracking of the position of theinstrument 5 can be realized by integrating active ultrasound sensorinto the distal tip. The ultrasound sensor transmits ultrasound wavesfrom within the vessel through the body of the patient 2 and a portionof the ultrasound signal is received by the intracorporal orextracorporal ultrasound imaging unit 3, which is also providing themorphological information of the target vasculature in its field ofview, enabling continuous localization of the distal tip 52 within thevessel morphology. Visualization of the position of the sensors 521,522and/or instrument 5 on the morphological representation 20 may beillustrated as in FIGS. 8a, 9a, 10a . A weakened segment of the vesselwall can be identified and tagged on the display by tracking theposition of the instrument with respect to the morphology of the vessel,and by knowing the phase difference between the pulsatile blood pressureand the pulsatile blood flow.

FIG. 12 illustrates schematically a method 100 of characterizing thecondition of the vessel wall of a patient. In step 101 the apparatus 6receives temporal pressure 621 and flow 622 measurement signals of apulsatile blood motion within the vessel, and in step 102 the processorof the apparatus 6 ascertains the phase difference 630,631 between thepulsatile blood pressure measurement signal 621 and the pulsatile bloodflow measurement signal 622, indicative of the condition of the vesselwall. Preferably, the sensors providing the measurement information areintegrated into the instrument 5 as shown in FIGS. 3 and 4, such as toprovide blood pressure 621 and blood flow 622 measurements in the sametransversal plane 526 of the instrument. The pressure and blood flowmeasurements may alternatively be performed with an instrument as shownin FIG. 2, where the two sensors are not providing measurements in thesame transversal plane of the vessel. As a consequence, the measurementof either the blood pressure or that of the blood flow has to becompensated for the phase offset originating from the known distancebetween the two sensors 521,522 integrated into the distal tip 52.Alternatively, two different instruments may be inserted into thevessel, each one comprising a single sensor, hence the pressuremeasurement can be carried out with a pressurewire (e.g. Verrata® fromVolcano Corporation), and the blood flow can be measured with a Dopplerguidewire (e.g. FloWire® from Volcano Corporation). In an embodiment ofthe method, the pressure is measured with a pressurewire and the bloodflow is measured with an imaging unit 3 related to one of the blood flowimaging modalities RA, CTA, MRA, UI. The method further comprises thestep 103 of rendering a representation of the phase difference 630between the pulsatile blood pressure measurement signal 621 and thepulsatile blood flow measurement signal 622 on a display 61, indicativeof the condition of the vessel wall. In step 104 the processor of theapparatus 6 is configured to render a morphological representation 20 ofthe vessel on the display 61 from the morphological information providedby the imaging unit 3. In step 105 the imaging unit 3 is tracking theposition of the instrument 5 with respect to the morphology of thevessel, and in step 106 the position of the instrument 5 is displayed onthe morphological representation 20 of the vessel.

In an embodiment of the method 100, the temporal pressure 621 and flow622 measurement signals originate from a vessel comprising an aneurysm14 in the vessel wall, and the measurement signals originate distal tothe aneurysm 14 with respect to a direction of the blood flow.Measurements proximal to the aneurysm would potentially show no phasedifference between the pulsatile pressure and blood flow, indicative ofhealthy vessel wall, unless yet another aneurysm is present proximal tothe respective measurement location. The method allows detection ofvessel wall weakness along the vessel during pullback of the instrument5 comprising both pressure and flow sensors, or by pulling back theinstrument comprising only the pressure sensor and by measuring theblood flow with the imaging unit 3 along the tracked trajectory of thepulled back instrument. The pullback rate should be such to allowsufficient time to determine the potential presence of phase difference630 in the discrete measurement locations along the pullback trajectoryof the instrument.

In an embodiment, the method 100 is used for assessing the efficacy offlow diverting stent 16 apposition. The flow diverting stent obstructsat least partially blood flowing into the aneurysm in order to reducethe cyclical pressure stretching the aneurysm wall. Reduction of bloodflow into the aneurysm also promotes intra-aneurysmal thrombosis. Anaccurate apposition of the flow diverting stent is detectable by asignificant reduction of post apposition phase difference 631 betweenthe pulsatile pressure 621 and pulsatile blood flow 622 measurementsignals with respect to the phase difference 630 prior to stentapposition.

The method 100 may be used for assessing efficacy of flow divertingstent 16 apposition after an initial treatment of coil 17 placement intothe aneurysm 14. A potential weakness of the treatment with coils isthat on a longer term the vessel wall in the vicinity of the initialneck 15 of the aneurysm may further weaken. A correctly appositionedstent protects the neck 15 of the aneurysm 14 and also the vessel wallin the vicinity proximal and distal to the aneurysm neck 15.

In an embodiment of the method 100, the temporal pressure 621 and flow622 measurement signals preferably originate at the same distance fromthe neck 15 of the aneurysm 14, with the advantage that there is notemporal offset caused by the dissimilar distances between the locationsof the pressure and blood flow measurements with respect to the aneurysmneck 15.

Although medical device was used in the exemplary description of theinvention, that should not be construed as limiting the scope.

Other variations to the disclosed embodiments can be understood andeffected by those skilled in the art in practicing the claimedinvention, from a study of the drawings, the disclosure, and theappended claims.

A single unit or device may fulfill the functions of several itemsrecited in the claims. The mere fact that certain measures are recitedin mutually different dependent claims does not indicate that acombination of these measures cannot be used to advantage.

In the claims, the word “comprising” does not exclude other elements orsteps, and the indefinite article “a” or “an” does not exclude aplurality.

Any reference signs in the claims should not be construed as limitingthe scope.

1. A system comprising: an apparatus for characterizing a condition of avessel wall of a living being; an instrument configured for providing atemporal pressure measurement signal of the pulsatile blood motionwithin the vessel when the instrument is inserted into the vessel; animaging unit configured for providing morphological information of thevessel and for tracking a position of the instrument with respect to themorphology of the vellel; wherein, the apparatus comprising: a processoris configured to: receive the temporal pressure measurement signal fromthe instrument and a temporal flow measurement signal of the pulsatileblood motion within the vessel; ascertain a phase difference between thetemporal pressure measurement signal and the temporal flow measurementsignal, indicative of the condition of the vessel wall.
 2. The systemaccording to claim 1, wherein the imaging unit is configured forproviding the temporal flow measurement signal of the pulsatile bloodmotion within the vessel.
 3. The system according to claim 2, furthercomprising a display, wherein the processor is configured for renderinga representation of the phase difference between the temporal pressuremeasurement signal and the temporal flow measurement signal on thedisplay, indicative of the condition of the vessel wall.
 4. The systemaccording to claim 3, wherein the processor is configured for renderinga morphological representation of the vessel on the display.
 5. Aninstrument usable in a system according to claim 1 and configured forinsertion into the vessel for providing temporal pressure and flowmeasurement signals of a pulsatile blood motion within a vessel,connectable to the apparatus and wherein the instrument comprises thepressure sensor and the flow sensor, located such as to provide temporalpressure and flow measurements in a same transversal plane of theinstrument, wherein the position of the instrument is trackable by theimaging unit with respect to the morphology of the vessel.
 6. A methodof characterizing a condition of a vessel wall of a living being, themethod comprising: inserting an instrument into the vessel; receivingtemporal pressure measurement signals of a pulsatile blood motion withina vessel from the instrument; receiving temporal flow measurementsignals of the pulsatile blood motion within the vessel: providingmorphological information of the vessel; tracking a position of theinstrument with respect to the morphology of the vessel; ascertaining aphase difference between the temporal pressure measurement signal andthe temporal flow measurement signal, indicative of the condition of thevessel wall.
 7. The method according to claim 6, further comprising:rendering a representation of the phase difference between the temporalpressure measurement signal (621) and the temporal flow measurementsignal on a display, indicative of the condition of the vessel wall. 8.The method according to claim 7, further comprising: rendering amorphological representation of the vessel on the display.
 9. The methodaccording to claim 8, further comprising: displaying (106) the positionof the at least an instrument (5) on the morphological representation(20) of the vessel (12).
 10. The method according to claim 9, comprisingpositioning of the instrument distal to an aneurysm with respect to adirection of the blood motion within the vessel based on tracking theposition of the instruments with respect to the morphology of thevessel.
 11. The method according to claim 10, comprising: positioning ofthe instrument distal to a flow dicerting stent impeding at leastpartially blood flowing into an aneurysm based on tracking the positionof the instruments with respect to the morphology of the vessel.
 12. Themethod according to claim 11, wherein the method is used for the vesselcomprising coils inside the aneurysm.
 13. The method according to claim11, wherein the temporal pressure and flow measurement signals areoriginating at a same distance from a neck of the aneurysm based ontracking the position of the instruments with respect to the morphologyof the vessel.
 14. The system according to claim 1, wherein theinstrument is configured for providing the temporal flow measurementsignal of the pulsatile blood motion within the vessel when theinstrument is inserted into the vessel.
 15. The system according toclaim 1, wherein the system is configured to acquire the temporalpressure measurement signal and the temporal flow measurement signal ofthe pulsatile blood motion in a same transversal plane of the vessel 16.The system according to claim 1, wherein the system is configured toacquire the temporal pressure measurement signal and the temporal flowmeasurement signal of the pulsatile blood motion along a trajectory ofthe instrument during a pullback motion within the vessel, and whereinthe processor is configured to ascertain the phase difference betweenthe temporal pressure measurement signal and the temporal flowmeasurement signal at discrete measurement locations along the pullbacktrajectory of the instrument.
 17. The method according to claim 6,wherein: receiving temporal pressure measurement signals of thepulsatile blood motion within the vessel from the instrument is along atrajectory of the instrument during a pullback motion within the vessel;and ascertaining the phase difference between the temporal pressuremeasurement signal and the temporal flow measurement signal, indicativeof the condition of the vessel wall, is at discrete measurementlocations along the pullback trajectory of the instrument